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Metabolische und mitochondriale Myopathien

Metabolic and mitochondrial myopathies

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Zusammenfassung

Metabolische Myopathien umfassen eine breite Krankheitsgruppe erblicher Enzymdefekte in den verschiedenen Stoffwechselwegen der Skelettmuskulatur. Sie zeigen eine ausgeprägte phänotypische Variabilität der Krankheitssymptome und unterschiedliche Manifestationsalter, wobei häufig Symptome einer Belastungsintoleranz oder permanente Paresen erhoben werden können. Manche metabolische Myopathien, insbesondere die Mitochondriopathien, gehen mit einer multisystemischen Organbeteiligung einher. Die Diagnostik muss auf den Einzelfall abgestimmt und in stufenartiger Reihenfolge erfolgen. Primär sollten Blutuntersuchungen (CK-Messungen, Muskelbelastungstests und Bestimmung des Acylcarnitin-Spektrums) erfolgen, als zweiter Schritt die Muskelbiopsie für histologische und enzymologische Untersuchungen sowie molekulargenetische Spezialuntersuchungen, wobei nicht in allen Fällen der ursächliche Enzymdefekt aufzuklären ist. Auf der anderen Seite ist gerade bei Patienten mit einer Belastungsintoleranz durch eine sorgfältige Untersuchung eine Abgrenzung gegen andere Ursachen, insbesondere psychosomatische Erkrankungen, wichtig. Bleibt diese aus, besteht die Gefahr, die Symptomatik einer metabolischen Myopathie als somatoforme Störung einzustufen. Die Therapie ist meist symptomorientiert auszurichten, lediglich die Pompe-Erkrankung ist mit einer Enzymersatztherapie kausal behandelbar.

Abstract

Metabolic myopathies include a broad group of diseases involving inherited enzyme defects in the various metabolic pathways and skeletal musculature. They show an extensive phenotypic variability of symptoms and different ages of manifestation. Symptoms often included intolerance to duress or permanent paresis. Some forms of metabolic myopathy, in particular mitochondriopathy, are associated with multsystemic organ participation. The diagnostics must be adjusted to individual cases and carried out in stages. Primary investigations should include blood parameters (e.g. creatine kinase measurement, muscle load tests and determination of the acylcarnitine spectrum) and a second step includes muscle biopsy for histological and enzyme investigations and special molecular genetic tests although the causative enzyme defect cannot be clarified in every case. On the other hand by means of a thorough investigation it is particularly important in patients with load intolerance to differentiate between other causes, in particular psychosomatic diseases. If this is not done there is a danger of classifying the symptoms of a metabolic myopathy as a somatoform disorder. Therapy is mostly symptom-oriented as Pompe disease is the only one which can be treated with enzyme replacement therapy.

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Abbreviations

AMP:

Adenosinmonophosphat

ATP:

Adenosintriphosphat

CK:

Creatinkinase

CPT:

Carnitin-Palmityl-Transferase

CPEO:

Chronisch progressive externe Ophthalomoplegie

ETF:

Elektrontransfer-Flavoprotein

ETF:QO:

Elektrontransfer-Flavoprotein:Ubiquinon-Oxidoreduktase

GAA:

α-1,4-Glukosidase

GSD:

Glykogenspeicherkrankheit

LDH:

Lactatdehydrogenase

MADD:

Multipler Acyl-CoA-Dehydrogenase-Mangel

MCAD:

Medium-chain-Acyl-CoA-Dehydrogenase

MCT:

Medium-chain-Triglyzeride

MELAS:

Mitochondriale Enzephalomyopathie mit Laktatazidosen und schlaganfallähnlichen Episoden

MERRF:

Myoklonusepilepsie mit „ragged-red fibers“

MNGIE:

Mitochondriale neurogastrointestinale Enzephalomyopathie

mtDNA:

Mitochondriale DNA

PCr:

Phosphokreatin

PFK:

Phosphofructokinase

PNP:

Polyneuropathie

SANDO:

Sensible Ataxia, Neuropathie, Dysarthrie, Ophthalmoplegie

VLCAD:

Very-long-chain-Acyl-CoA-Dehydrogenase

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Interessenkonflikt

Der korrespondierende Autor weist für sich und seinen Koautor auf folgende Beziehungen hin: Die Autoren erhielten in den vergangenen 3 Jahren Honorare für Vortragstätigkeiten und Fortbildungen von Genzyme GmbH, Neu-Isenburg.

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Authors and Affiliations

  1. Neurologische Universitätsklinik, Muskelzentrum Ruhrgebiet, Kliniken Bergmannsheil, Ruhr-Universität Bochum, Bürkle-de-la Camp-Platz 1, 44789, Bochum, Deutschland

    M. Vorgerd

  2. Neurologische Universitätsklinik, Martin-Luther Universität Halle-Wittenberg, Halle (Saale), Deutschland

    M. Deschauer

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  1. M. Vorgerd
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  2. M. Deschauer
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Correspondence to M. Vorgerd.

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Vorgerd, M., Deschauer, M. Metabolische und mitochondriale Myopathien. Z. Rheumatol. 72, 242–254 (2013). https://doi.org/10.1007/s00393-012-1082-9

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